Two radionuclide imaging methods will be developed and applied clinically to evaluate myocardial ischemia and infarction. These methods are: (1) Serial imaging after a single dose of thallium-201 and (2) Imaging of radiolabeled cardiac myosin specific antibody. Preliminary data suggest that comparison of initial distribution and redistribution of 201Tl can distinguish between viable underperfused and nonviable infarcted myocardium. Cell membrane permeability to large molecules is a sign of severe damage. Uptake of antibody to cardiac myosin is evidence of severe cell membrane damage: and may be a highly specific indicator of myocardial infarction. This proposal, therefore, seeks to determine the mechanism of localization of 201Tl and anti-myosin antibody and the factors which affect that localization in normal, ischemic, and infarcted myocardium. Studies will be carried out on several levels: in vitro (Section 1); in pure myocyte (Part A) and intact heart organ culture (Part B); in canine (Section 2); and in man (Section 3). Utimately when completed, these studies would not only define the clinical utility of the techniques described, but would also define the basic mechanisms reponsible for their uptake. It is anticipated that application of serial imaging after 201Tl would allow early differentiation of ischemia and infarction, while imaging of labeled antibody to cardiac myosin would be a specific indicator of acute myocardial infarction.